Capillary printing systems

ABSTRACT

The invention provides printing systems and methods for depositing small volumes of liquid on solid substrates. These systems and methods are useful with a wide variety of liquids and substrates and offer a wide variety of applications, including the deposition of arrays of analytes. In particular embodiments, the systems comprise a preservation device, a detachable ganged plurality of printing devices, and/or a wire bonding capillary.

FIELD OF THE INVENTION

[0001] The invention is in the field of capillary printing systems andtheir fabrication.

BACKGROUND

[0002] The accurate dispensing and deposition on a substrate of smallvolumes of liquid has been effected with a variety of printinginstruments including micropipettes and injectors (see, e.g. U.S. Pat.Nos. 4,815,325; 5,601,980; 5,747,102), ink-jet printers (see, e.g. U.S.Pat. No. 5,338,688), and fountain-pen type contact-depositioncapillaries (see, e.g. WO95/35505 and U.S. Pat. No. 5,770,151). Inaddition, a number of multiport liquid transfer and delivery apparatusesare commercially available (e.g. MICROLAB® DNA Workstation by HamiltonCo., Reno, Nev.; HYDRA Microdispenser by Robbins Scientific, Sunnyvale,Calif.; Microarray Printing System by Genometrix, The Woodlands, Tex.).While some of these instruments have been used to print orderedanalytical or probe arrays, they offer various relative advantages anddisadvantages, including differing print resolution, speed,cross-contamination control, probe tolerances, etc. For example, thecartridges utilized in ink-jet printers dispense a controlled volume ofliquid by use of a pressure wave created within the cartridge and whichresults from a sharp temperature increase to the ink that can damage orsheer a molecularly fragile probe. Existing pipettors and contactdeposition capillaries are better suited to printing fragile probes butrequire washings between different probe loadings and offer limitedprint resolution. The present invention provides improved printingsystems particularly suited for printing high-density analytical arrays.

SUMMARY OF THE INVENTION

[0003] The invention provides printing systems and methods fordepositing small volumes of liquid on solid substrates. These systemsand methods are useful with a wide variety of liquids and substrates andoffer a wide variety of applications, including the deposition of arraysof analytes, such as chemical and biochemical library arrays.

[0004] In one embodiment, the invention provides a printing systemcomprising a pod, a detachable printing device, a substrate, apositioner and a preservation device, wherein (a) the pod comprises areceptacle for reversibly attaching an attachment portion of theprinting device; (b) the printing device comprises a reservoircontaining a liquid comprising a predetermined agent and in fluidconnection with the reservoir, a capillary comprising an axial borehaving proximal and distal openings to ambient pressure and a printingtip comprising the distal opening and which prints the agent on thesubstrate; (c) the positioner moves the pod relative to the substrate;and (d) the preservation device is within, containing or in contact withthe printing device and preserves the capability of the printing deviceto print the agent on the substrate over long-term storage. Generally,the preservation device provides a deterrent to evaporation of theliquid, such as a hermetic barrier, a refrigerator, a humidifier, ahygroscopic agent, etc. The system may also comprise a detachable gangedplurality of such printing devices.

[0005] In another embodiment, the invention provides a printing systemcomprising a pod, a detachable ganged plurality of printing devices, asubstrate and a positioner, wherein (a) the pod comprises a receptaclefor reversibly attaching an attachment portion of the printing devices;(b) each of the printing devices comprises a reservoir containing aunique agent and in fluid connection with the reservoir, a capillarycomprising an axial bore having proximal and distal openings to ambientpressure and a printing tip comprising the distal opening and whichprints the agent on the substrate; and (c) the positioner moves the podrelative to the substrate.

[0006] In another embodiment, the invention provides a printing systemcomprising a wire bonding capillary containing a predetermined agent andcomprising an axial bore having proximal and distal openings to ambientpressure and a printing tip comprising the distal opening and whichprints the agent. And in a more particular embodiment, the inventionprovides a printing system comprising a ganged plurality of wire bondingcapillaries, each containing a different agent and comprising an axialbore having proximal and distal openings to ambient pressure and aprinting tip comprising the distal opening and which prints the agent.

[0007] A wide variety of more particular embodiments of these systemsare disclosed. For example, in one such embodiment, the capillary boretapers toward the distal opening of the tip; in another, the systemfurther comprises a motion resistor operatively joined to the capillaryand providing an incomplete resistance to motion of the capillary alongits longitudinal axis, wherein the resistance may be provided bysprings, an elastomeric membrane, the weight of the capillary, etc.; inanother, the printing device is of one-piece construction; in another,the system further comprises a register comprising a guide whichcontacts a registration portion of the printing device, distal to theattachment portion, and moves the tip relative to the substrate; etc.

[0008] The invention provides methods of making, using and storing thesubject systems including methods for printing liquids comprising agentsor analytes on substrates with the printing systems, particularlyprinting methods which comprise the step of decelerating the capillaryto move the liquid through the bore, out the tip and onto the substrate,which method may be effected, for example, by tapping the tip onto thesubstrate.

BRIEF DESCRIPTION OF THE DRAWINGS

[0009]FIG. 1 shows a schematic of a printing head providing a gangedplurality of printing devices.

[0010]FIG. 2 shows a schematic of a spring block motion resistor, aprinting head and a registration plate.

[0011]FIG. 3 shows a schematic of a single printing device in thecontext of spring block motion resistor, printing head and registrationplate portions.

[0012]FIG. 4 shows a schematic of a plurality of printing devices in thecontext of block motion resistor, elastomeric sheet and printing headportions.

[0013]FIG. 5 shows a schematic of a single printing device in thecontext of foam plug spring block motion resistor and printing headportions.

[0014]FIG. 6 shows a schematic of an inserted capillary printing deviceand a machined in printing device in the context of plunger-bearingspring block motion resistor and printing head portions.

[0015]FIG. 7 shows a schematic of a printing head portion havingcompressable channel walls.

[0016]FIG. 8 shows a schematic of a single-piece construction lowdensity multi-chanel printing head.

[0017]FIG. 9 shows a schematic of a single-piece construction highdensity multi-chanel printing head.

[0018]FIG. 10 shows schematic of a registration plate and a printinghead comprising a floppy door preservation device.

[0019]FIG. 11 shows schematic of a registration plate housing a printinghead comprising a floppy door preservation device with the door opened.

[0020]FIG. 12 shows a schematic of an open jewel box type preservationdevice housing a printing head.

[0021]FIG. 13 shows a schematic of a closed caddy box type preservationdevice housing a printing head.

[0022]FIG. 14 shows a schematic of an open caddy box type preservationdevice housing a printing head.

[0023]FIG. 15 shows a schematic of a spring block and an open pop-outbox type preservation device housing a printing head.

[0024]FIG. 16 shows a schematic of a spring block depressing theprinting head of an open pop-out box type preservation device.

[0025]FIG. 17 shows a schematic of a open, passive loading, vaccumevacuation printing tip system.

[0026]FIG. 18 shows a schematic of a valve-actuated, passive loading,vaccum evacuation, presure purging printing tip system.

[0027]FIG. 19 shows a schematic of a valve-actuated, active loading,vaccum evacuation, presure purging printing tip system.

[0028]FIG. 20 shows a schematic of a gravity or pressure loading, activepurging printing tip system.

[0029]FIG. 21 shows a schematic of a high-throughput a printing system.

DETAILED DESCRIPTION OF PARTICULAR EMBODIMENTS OF THE INVENTION

[0030] The following descriptions of particular embodiments and examplesare offered by way of illustration and not by way of limitation.

[0031] In a first aspect, the invention provides a printing systemcomprising a pod, a detachable printing device, a substrate, apositioner and a preservation device, wherein (a) the pod comprises areceptacle for reversibly attaching an attachment portion of theprinting device; (b) the printing device comprises a reservoircontaining a liquid comprising a predetermined agent and in fluidconnection with the reservoir, a capillary comprising an axial borehaving proximal and distal openings to ambient pressure and a printingtip comprising the distal opening and which prints the agent on thesubstrate; (c) the positioner moves the pod relative to the substrate;and (d) the preservation device is within, containing or in contact withthe printing device and preserves the capability of the printing deviceto print the agent on the substrate over long-term storage. This systemis specifically adapted for long-term storage of the printing device andis amenable to a wide variety of suitable pods, detachable printingdevices, substrates, positioners, preservation devices, applications andmore particular embodiments.

[0032] Suitable pods include any structural member that transfers thepositioning of the positioner to the printing device through areceptacle for reversibly attaching an attachment portion of theprinting device. For example, the pod may simply be the terminus of amechanical arm of the positioner with an engaging recess for receivingthe proximal (distal from the tip) end of a capillary printing device.

[0033] Suitable printing devices include any structural member whichcombines by fluid connection the requisite reservoir and capillary. Forexample, the printing device may simply be a capillary comprising aliquid-filled bore having a proximate reservoir portion and terminatingat a distal portion comprising the printing tip. Alternatively, thereservoir may comprise a more voluminous non-capillary liquid filledchamber having a relatively larger internal diameter in fluid connectionwith a capillary comprising the printing tip. The reservoir portion ofthe printing device is adapted to contain and contains a liquidcomprising a predetermined agent. The device may be made of anyconvenient and compatible material. For example, suitable capillaryfabrication material ceramic, silicons, glasses, etc. The printingdevice is adapted or adaptable to contain, store and/or print a widevariety of liquids, including aqueous liquids, liquids comprisingorganic polar solvents such as alcohols, DMSO, acetonitrile, etc.,nonpolar solvents such benzene, chloroform, etc.

[0034] Suitable substrates include any material providing a suitableprinting surface, and include sheets of glasses, ceramics, plastics,metals, silicons, acetate, cellulose (paper), etc. The substrate mayprovide a homogeneous surface or a surface offering differential surfacechemistry, topography, etc. For example, the surface may offerpredetermined printing sites adapted to receiving, binding, reacting,containing and/or retaining the printing fluid.

[0035] Suitable positioners include any device which provides therequisite positioning of the printing device to effect the desiredprinting sites on the substrate. Frequently, the positioner will providea first positioning within the two-dimensional plane of the substratesurface and a second positioning perpendicular to the surface to effectcontact printing on the surface. The positioner is generallyelectomechanically operated by a computer controlled robot.

[0036] Generally, the preservation device of these systems provides adeterrent to evaporation of the liquid, such that printing can beinterrupted for extended periods, such as days, preferably weeks, morepreferably months and even years, and then resumed without reloading theprinting device. In various embodiments, the systems suffer less than a50%, preferably less than a 20%, more preferably less than a 5%degradation in printing capacity over the storage period, as measured bysubsequent error or misprint frequency, fluid loss, etc., as comparedwith an otherwise comparable but uninterrupted system. A wide variety ofsuitable preservation devices may be used. In one example, the devicecomprises a hermetic barrier, such as a seal on the printing device or acontainer capable of receiving and housing the printing device, whichprovides a system that is relatively, preferably substantially, morepreferably fully closed to the printing solvent liquid and vapor. Thesebarrier or containment devices may also provide a solvent vapordistributor, such as an absorbent sponge wetted with the solvent of theprinting fluid, within the closed system to further minimizeevaporation. In another example, the device comprises a refrigerator tocool or preferably freeze the liquid in the capillary of the printingdevice. In yet another example, the device comprises a hygroscopic agentwhich is incorporated in the liquid in the capillary and reduces thevolatility of the liquid. For example, where the solvent of the liquidis water, suitable agents include glycerol (e.g. 5-95%), salts, etc.

[0037] The printing system is adaptable to virtually any application ofsmall volume, high resolution liquid printing. For example, a widevariety of chemical and biochemical libraries may be deposited,including libraries derived from random or directed synthetic schemes,natural products including genetic material, etc. A particularapplication is the deposition of high density arrays of biochemicalreagents or analytes such as polypeptides and polynucleotides (polymersof amino acids and nucleotides, preferably at least 5, more preferablyat least 15, more preferably at least 50, more preferably at least 150monomer units in length), e.g. for effecting solid phase, preferablyhigh throughput solid phase immuno assays and hybridization assays.

[0038] More particular embodiments of this system include systemswherein the dimensions and composition of the printing device capillarybore interact with the fluid contained therein to maintain the fluidproximate to the distal opening of the capillary tip. For example, thecapillary bore may be tapered, preferably conically tapered toward thedistal opening of the tip.

[0039] In another more particular embodiment, the system furthercomprises a motion resistor operatively joined to the capillary andproviding an incomplete resistance to motion of the capillary along itslongitudinal axis, wherein the resistance may be provided by springs, anelastomeric membrane, the weight of the capillary, etc. Such a motionresistor is especially important to facilitate contact printing onrelatively planar or flat surfaces, especially wherein the systemcomprises a plurality of printing devices which print in concert,wherein the resistor(s) permit simultaneous contact of the printingdevices on the surface.

[0040] In another more particular embodiment, the printing device is ofone-piece construction and/or comprises a wire bonding capillary,described below. The system may also comprise a detachable gangedplurality of printing devices.

[0041] In another more particular embodiment, the system furthercomprises a register comprising a guide which contacts a registrationportion of the printing device, distal to the attachment portion, andmoves the tip relative to the substrate; etc. A wide variety ofregisters are provided. A printing system comprising a register mayfurther comprise first and second detachable printing capillariescomprising respective first and second probes, a pod comprising areceptacle for attaching one of the capillaries, a substrate upon whichthe capillaries deposit the probes, whereupon detachment of the firstcapillary and attachment of the second capillary after deposition of afirst portion of a high density probe array by the first capillary onthe substrate, the register is capable of positioning the secondcapillary at a sufficiently similar position relative to the substrateto permit deposition of a second portion of the array by the secondcapillary on the substrate. In this system, the capillaries and probesmay be different or the same.

[0042] In a second aspect, the invention provides a printing systemcomprising a pod, a detachable ganged plurality of printing devices, asubstrate and a positioner, wherein (a) the pod comprises a receptaclefor reversibly attaching an attachment portion of the printing devices;(b) each of the printing devices comprises a reservoir containing aunique agent and in fluid connection with the reservoir, a capillarycomprising an axial bore having proximal and distal openings to ambientpressure and a printing tip comprising the distal opening and whichprints the agent on the substrate; and (c) the positioner moves the podrelative to the substrate. This system provides a wide variety of waysof ganging a plurality of printing devices. In one embodiment, thedetachable ganged plurality comprises a block having receptacles orholes for and which laterally constrain each of the printing devices.Alternatively, a rigid or elastomeric band or clamp may be used to gangtogether the printing devices. In a preferred embodiment, these systemsprovide analyte-specific dedicated printing devices.

[0043] In another embodiment of this aspect of the invention, aone-piece block fabricated from a single material element provides thedetachable ganged plurality, increasing the precision, accuracy,repeatability, reliability, speed and permitted densities of spotdeposition. Because it is made from a single material element thisdevice is also easier and less expensive to construct and maintain. Awide variety of standard microlithography, micromachining and/ormicrofabrication methods known to those in the art may be used toconstruct these devices including injection molding, embossing, etchingmethods such as deep reaction ionic etching (DRIE), electric dischargemachining (EDM), deposition, computer numerical control (CNC) milling,etc. Accordingly, the devices may be manufactured from a wide variety ofmaterials depending on the selected manufacturing method, includingplastics such as polycarbonate, polystyrene, polypropylene and PMMA;glasses and/or ceramics; semiconductor material such as silicon; andmetals such as stainless steel. The devices may be constructed in avariety formats in terms of nozzle density, head size, reservoir size,etc. Print precision and accuracy are provided by precision engineeringspecifications including: nozzle surface (e.g. flatness) variation ofless than 10, preferably less than 5, more preferably less than 2, morepreferably less than 1 um across all the nozzle tips of a head andinternozzle print volume and distance (center-to-center) variation ofless than about 4, preferably less than about 2, more preferably lessthan 1, more preferably less than 0.5%. The nozzles may be spaced toprovide direct loading from standard microtiter sample plates (e.g. 9 mmcenter-to-center) or at higher densities wherein the reservoirs may beloaded with conventional microvolume liquid handling devices. In aparticular embodiment, the nozzles are spaced to correspond with thedesired array density, avoiding the need for off-set printing.

[0044] In a third aspect, the invention provides a printing systemcomprising a wire bonding capillary containing a predetermined agent andcomprising an axial bore having proximal and distal openings to ambientpressure and a printing tip comprising the distal opening and whichprints the agent. Wire bonding capillaries are adapted fromsemiconductor manufacturing, where a wire bonding process is used toelectrically connect metal bond pads formed on a semiconductor die tothe leadfingers of a leadframe. In this process, a bond wire is threadedthrough a wire bonding capillary and the end of the wire protrudingthrough the capillary tip is heated to a molten ball. The molten ball isthen mechanically pressed by the bonding capillary against the heatedbond pad to alloy the metallic elements of the wire and bond pad. Thecapillary is then moved to a bonding site on the designated leadfingerwhere the wire is pressed against the heated leadfinger to bond thewire, then tensioned and sheared. Wire bonding capillaries are wellknown in the semiconductor manufacturing art, are the subject ofnumerous publications and patents (see e.g. U.S. Pat. Nos. 3,894,671;4,877,173; 5,082,154; 5,558,270; 5,662,261) and are commerciallyavailable from a number of sources (e.g. Micro-Swiss of Kulicke & SoffaIndustries, Inc., Willow Grove, Pa.; Gaiser Tool Company, Ventura,Calif.; Small Precision Tools, Petaluma, Calif., etc.)

[0045] In a more particular embodiment, the invention provides aprinting system comprising a ganged plurality of wire bondingcapillaries, each containing a different agent and comprising an axialbore having proximal and distal openings to ambient pressure and aprinting tip comprising the distal opening and which prints the agent.

[0046] The invention provides methods of making, using and storing thesubject systems including methods for printing liquids comprising agentsor analytes on substrates with the printing systems, particularlyprinting methods which comprise the step of decelerating the capillaryto move the liquid through the bore, out the tip and onto the substrate,which method may be effected, for example, by contact printing, e.g.tapping the tip onto the substrate. A wide variety of methods may beused for loading and/or unloading the printing devices, includingpassive capillary loading and unloading from the printing tip,vacuum-assisted unloading, active pressure purging, etc. Uninterruptedmult-head printing systems comprising 25 20×20 (400 nozzle) headsprovide for offset printing 10,000 spot arrays on chip substrates atrates of at least 0.2 chips/sec., preferably 1 chip/sec., morepreferably at least 5 chips/sec.

EXAMPLES

[0047] Referring to FIG. 1, a plurality of printing devices 11 are shownhoused in receptacles of a gang 12 comprising tabs 13 for attaching to apod (not shown) of a printing system.

[0048] Referring to FIG. 2, a plurality of printing devices 11 are shownhoused in receptacles of a gang print head 12 comprising tabs 13. Abovethe print head 12 is a spring block 21 retaining a plurality of verticalactuators 22. Below the print head 12 is a registration plate 23comprising a plurality of registration apertures 24.

[0049] Referring to FIG. 3, a printing device 11 is shown housed in areceptacle of a portion of a print head 12. Above the portion of theprint head 12 is a portion of a spring block 21 is shown retaining avertical actuators 22 comprising a spring 31, a spring shaft 32comprising a vent 33. Below the portion of the print head 12 is aportion of the registration plate 23 comprising a registration aperture24.

[0050] Referring to FIG. 4, a plurality of printing devices 11 are shownhoused in receptacles of a portion of a print head 12. Above the portionof the print head 12 is a spring and vent cavity block 41 and betweenthe block 41 and the print head 12 is a punch vented latex spring sheet42.

[0051] Referring to FIG. 5, a printing device 11 is shown housed in areceptacle of a portion of a print head 12. Above the portion of theprint head 12 is a portion of a spring and vent cavity block 41 is shownretaining a quick-recovery open cell foam spring/vent combination 51.

[0052] Referring to FIG. 6, an inserted capillary printing device 61 anda machined in printing device 62 are shown housed and formed,respectively, in receptacles of a portion of a print head 12. Above theportion of the print head 12 is a spring block 63. The spring block 63contains spring-loaded plungers 64, each comprising a spring 65, aflange 66 and a shaft 67, and positioned above the printing devices 61and 62.

[0053] Referring to FIG. 7, a plurality of machined in printing devices62 are shown formed in receptacles of a portion of a print head 12,wherin the capillary portion 71 of the devices 62 have compressiblechannel walls 72.

[0054] Referring to FIG. 8, a single-piece construction low density(e.g. 64 tips/cm²) multi-chanel printing head 81 is shown incross-section. The head 81 comprises injection molded reservoirs 82 influid connection with the capillary bores 83 of molded printing tips 84.

[0055] Referring to FIG. 9, a single-piece construction high density(e.g. 400 tips/cm²) multi-chanel printing head 91 is shown incross-section. The head 91 comprises etched reservoirs 92 in fluidconnection with the capillary bores 93 of etched printing tips 94.

[0056] Referring to FIG. 10, a print head 12 with an operatively affixedclosed floppy door preservation device 101 is shown in approach toward aregistration plate 102 comprising a plurality of printing tipregistration apertures 103.

[0057] Refering to FIG. 11, a print head 12 with an operatively affixedopen floppy door preservation device 101 is shown in contact with aregistration plate 102 comprising a plurality of printing tipregistration apertures 103, wherein the open floppy door preservationdevice 101 is shown in a slide open orientation. In an alternativeembodiment, the open floppy door preservation device 101 may be swungopen.

[0058] Referring to FIG. 12, an open jewel box type preservation device121 containing a saturated foam pad 122 is shown housing a print head12.

[0059] Referring to FIG. 13, a closed caddy box type preservation device131 containing a saturated foam pad 122 is shown housing a print head12.

[0060] Referring to FIG. 14, an open caddy box type preservation device131 containing a saturated foam pad 122 is shown housing a print head12.

[0061] Referring to FIG. 15, a pop-out box type preservation device 151containing a saturated foam pad is 122 shown in open position housing aprint head 12. Above and approaching the print head 12 is shown a springblock 152.

[0062] Referring to FIG. 16, a pop-out box type preservation device 151containing a saturated foam pad is 122 shown in open position housing aprint head 12. Above and depressing the print head 12 is shown a springblock 152.

[0063] Referring to FIG. 17, a printing device 11 comprising a vent hole171 is shown housed in a linear bearing receptacle of a portion of aprint head 12. Below the portion of the print head 12 is a portion of avacuum plate 172 comprising a vacuum aperture 173.

[0064] Referring to FIG. 18, a printing device 11 is shown housed in alinear bearing receptacle of a portion of a print head 12. Below theportion of the print head 12 is a portion of a vacuum plate 172comprising a vacuum aperture 173. In fluid connection with the printingdevice 11 through tubing 181 is a three-way valve 182 alternativelyconnecting the device to atmospheric pressure, closure or pressurizednitrogen.

[0065] Referring to FIG. 19, a printing device 11 is shown housed in alinear bearing receptacle of a portion of a print head 12. Below theportion of the print head 12 is a portion of a vacuum plate 172comprising a vacuum aperture 173. In fluid connection with the printingdevice 11 through tubing 181 is are four two-way valves 191 parallel,alternatively connecting the device to closure or respectively,pressurized nitrogen, water, atmospheric pressure and vacuum.

[0066] Referring to FIG. 20, a printing device 11 is shown in fluidconnection through tubing 181 with a sample reservoir 201.

[0067] Referring to FIG. 21, a printing system 210 comprising amultihead printing assembly 211 rotatably attached to a multichipturntable 212. The assemby 211 comprises a plurality of single-piececonstruction high density (400 tips/cm²) multi-channel detachableprinting heads 91 joined to the assembly 211 through actuators 213 whichprovide positioning stages 214 and L-brackets 215 for attaching theprint heads 91. The turntable 212 provides chip recepticles 217 whichposition the chips 216 which provide a printing substrate. In operation,the actuators 213 simulateously stamp their respective printing heads 91on the corresponding chips 216. Thereafter, the turntable 212 rotatesone chip position and the necessary printing offset is effected byturntable 212 rotation, acutator 213 positioning, or both. As theprinting on a given chip 216 is completed (e.g. a complete array isdeposited), the chip 216 is removed from the turntable 212 and replacedwith a new chip 216, thereby providing uninterrupted printing.

[0068] All publications and patent applications cited in thisspecification are herein incorporated by reference as if each individualpublication or patent application were specifically and individuallyindicated to be incorporated by reference. Although the foregoinginvention has been described in some detail by way of illustration andexample for purposes of clarity of understanding, it will be readilyapparent to those of ordinary skill in the art in light of the teachingsof this invention that certain changes and modifications may be madethereto without departing from the spirit or scope of the appendedclaims.

What is claimed is:
 1. A wire bonding capillary containing a liquid. 2.A printing system comprising a printing device comprising a wire bondingcapillary containing a liquid, wherein the liquid comprises apredetermined agent and the capillary comprises an axial bore havingproximal and distal openings and a printing tip comprising the distalopening and which prints the agent.
 3. A printing system according toclaim 2 , wherein the liquid is aqueous.
 4. A printing system accordingto claim 2 , wherein the liquid comprises an organic polar solvent.
 5. Aprinting system according to claim 2 , wherein the liquid comprises anonpolar solvent.
 6. A printing system according to claim 2 , whereinthe agent is a polypeptide.
 7. A printing system according to claim 2 ,wherein the agent is a polynucleotide.
 8. A printing system according toclaim 2 , wherein the agent is a polynucleotide at least 50 nucleotidesin length.
 9. A printing system according to claim 2 , wherein the boretapers toward the distal opening of the tip.
 10. A printing systemaccording to claim 2 , wherein the capillary comprises a ceramicmaterial.
 11. A printing system according to claim 2 , wherein theproximal and distal openings are open to ambient pressure and the systemprints by decelerating the capillary to move the agent through the bore,out the tip and onto the substrate.
 12. A printing system according toclaim 2 wherein said capillary is one of a ganged plurality of wirebonding capillaries, each containing a different predetermined agent andeach comprising an axial bore having proximal and distal openings and aprinting tip comprising the distal opening and which prints the agent.13. A printing system according to claim 2 wherein said capillary is oneof a ganged plurality of wire bonding capillaries, each containing adifferent predetermined agent and each comprising an axial bore havingproximal and distal openings and a printing tip comprising the distalopening and which prints the agent, wherein the ganged pluralitycomprises a rigid or elastomeric band or clamp to gang together thecapillaries.
 14. A printing system according to claim 2 wherein saidcapillary is one of a ganged plurality of wire bonding capillaries, eachcontaining a different predetermined agent and each comprising an axialbore having proximal and distal openings and a printing tip comprisingthe distal opening and which prints the agent, wherein the gangedplurality comprises a block having receptacles for and which laterallyconstrain each of the capillaries.
 15. A printing system according toclaim 2 , further comprising a substrate on which the device prints theagent, the substrate selected from the group consisting of glass,ceramic, plastic, metal, silicon, acetate and cellulose.
 16. A printingsystem according to claim 2 , further comprising a substrate on whichthe device prints the agent, the substrate providing a homogeneoussurface.
 17. A printing system according to claim 2 , further comprisinga substrate on which the device prints the agent, the substrateproviding a surface offering differential surface chemistry ortopography.
 18. A printing system according to claim 2 , furthercomprising a substrate on which the device prints the agent, thesubstrate providing a surface offering differential surface chemistry ortopography, which provide predetermined printing sites adapted toreceiving, binding, reacting, containing or retaining the agent orliquid.
 19. A printing system according to claim 2 , wherein theprinting device further comprises a non-capillary chamber alsocontaining the liquid and having a relatively larger internal diameterthan and in fluid connection with the capillary.
 20. A printing systemaccording to claim 2 , wherein the printing device is detachable and thesystem further comprises a pod, a substrate and a positioner, wherein:the pod comprises a receptacle for reversibly attaching an attachmentportion of the printing device; the positioner moves the pod relative tothe substrate; and the printing device prints the agent on thesubstrate.
 21. A printing system according to claim 20 furthercomprising a motion resistor operatively joined to the capillary andproviding an incomplete resistance to motion of the capillary along itslongitudinal axis, biasing said motion toward the substrate, wherein theresistor is selected from a plurality of springs, an elastomericmembrane and the weight of the capillary.
 22. A printing systemaccording to claim 20 further comprising a motion resistor operativelyjoined to the capillary and providing an incomplete resistance to motionof the capillary along its longitudinal axis, biasing said motion towardthe substrate, wherein the resistor is the weight of the capillary. 23.A printing system according to claim 20 further comprising a registercomprising a guide which contacts a registration portion of the printingdevice, distal to the attachment portion, and moves the tip relative tothe substrate.
 24. A printing system according to claim 11 , furthercomprising a preservation device within, containing or in contact withthe printing device, which preserves the capability of the printingdevice to print the agent on the substrate over long-term storage of theprinting device, wherein the preservation device comprises a deterrentto evaporation of the liquid, wherein the deterrent is selected from thegroup consisting of a hermetic barrier, a refrigerator, a humidifier anda hygroscopic agent,
 25. A printing system according to claim 11 ,further comprising a preservation device within, containing or incontact with the printing device, which preserves the capability of theprinting device to print the agent on the substrate over long-termstorage of the printing device, wherein the preservation devicecomprises a deterrent to evaporation of the liquid, wherein thedeterrent is a hermetic barrier.
 26. A method for printing an agent on asubstrate comprising the step of printing an agent with the printingsystem of claim 2 .
 27. A method for painting an agent on a substratecomprising the step of printing an agent with the printing system ofclaim 8 .
 28. A method for printing an agent on a substrate comprisingthe step of printing an agent with the printing system of claim 11 . 29.A method for printing an agent on a substrate comprising the step ofprinting an agent with the printing system of claim 12 .
 30. A methodfor printing an agent on a substrate comprising the step of printing anagent with the printing system of claim 18 .
 31. A method for printingan agent on a substrate comprising the step of printing an agent withthe printing system of claim 20 .